Procedures such as hyperthermia, treatment of cardiac arrhythmias and heat sensitive promoters in gene therapy require temperature change monitoring. Magnetic resonance imaging (MRI) thermometry overcomes problems associated with invasive temperature monitoring techniques such as thermocouples and fiber optics. In the current MRI thermometry the temperature variation is detected by measuring small changes in the proton resonant frequency, longitudinal relaxation time or apparent diffusion coefficient. However, these techniques have low temperature sensitivity and influenced by the local motion and magnetic susceptibility variation. This R21 application is directed to a noninvasive thermometry monitoring system for determining a temperature of tissue to which hyperthermia treatment is administered. The noninvasive thermometry monitoring system uses magnetic nanoparticles having a known magnetic moment profile that correlates with temperatures. In hyperthermia treatment, the noninvasive thermometry monitoring system may be used to determine whether the target tissue is being heated as desired and to what temperature the target tissue is being heated. We have developed magnetic nanoparticles that have been demonstrated as hyperthermia agent and anti-cancer drug targeted delivery agents. With the assessment of an applied magnetic field the same particles have also demonstrated the ability to prolong the delivery of its anti-cancer agent to tumors. However, a major technical challenge that has not been effectively met is the ability to monitor the effectiveness and progress of the hyperthermia treatment. The overall aim of this exploratory research application is to evaluate the feasibility of MRI-thermometry monitoring during hyperthermia therapy. The long-term goal of this research program is to integrate existing complementary modalities of diagnosis and therapy with safe multifunctional nanoparticles that will enable non-invasive monitoring and guiding of interventions without having to change the environment. The proposed exploratory research has two specific aims. The first specific aim is to evaluate the contrast ability of the hyperthermia magnetic nanoparticles in ex vivo with parameters that simulate patient testing conditions. The second specific aim is to develop thermometry (temperature contour) based on the MRI contrast imaging experiments. It is anticipated that upon the successful completion of this exploratory research project a subsequent project will be initiated to evaluate the MRI-guided magnetic hyperthermia therapy in an animal model.